We propose to conduct a prospective investigation to assess whether infection with the Epstein-Barr Virus or Chlamydia pneumoniae increases the risk of multiple sclerosis (MS). For this purpose we have identified two large populations of individuals whose blood samples were collected and stored several years ago and are available fore analyses, and we are in the process of documenting cases of MS that occurred in these populations after the date of blood collection. One population comprises over 3 million US Army personnel whose blood samples are stored in the Department of Defense (DOD) Serum Repository; the other comprises 125,000 participants in the Kaiser Permanente Health Plan (KPHP), whose blood samples were collected over 20 years ago. The identification and diagnostic confirmation of the cases of MS occurring in these populations has already been funded in part by a pilot grant from the National Multiple Sclerosis Foundation. Based on our preliminary work, we estimate that we will be able to document 216 cases of MS with onset after the date of collection of the stored serum samples. Main hypotheses to be addressed are that risk of MS is increased among individuals infected with EBV or C pneumoniae, as determined by the presence of specific serum antibodies, and that elevated antibody titers against EBV or C pneumoniae antigens predate the onset of MS.